Polyketides are a diverse class of naturally occurring molecules typically produced by a variety of organisms, including fungi and mycelial bacteria, in particular actinomycetes. Although polyketides have widely divergent structures, they are classified together because they all share a common biosynthetic pathway in which the carbon backbone of these molecules are assembled by sequential, step-wise addition of two carbon or substituted two carbon units referred to as ketides. Polyene polyketides comprise a chain of ketide units that have been strung together by a series of enzymatic reactions by multimodular polyketide synthase proteins.
Polyketides are usually found in their natural environment only in trace amounts. Moreover, due to their structural complexity, polyketides are notoriously difficult to synthesize chemically. Nevertheless, polyene oxazole polyketides have been shown to exhibit antibacterial and antiviral activities. Curromycin A and B have been reported to possess antibacterial activity (Ogura et al., J. Antibiotics, Vol. 38, No. 5, 669-673 (1985); M. Ogura et al, Agric. Biol. Chem., Vol. 49, No. 6, 1909-1910 (1985). Oxazolomycins have also been reported to exhibit antibacterial, antiviral and also in some cases, antitumor activity against P388 leukemia cells (Kansaki et al., Biosc. Biotechnol. Biochem., Vol. 62, No. 3, 438-442 (1998); Mori et al., Tetrahedron Letters, Vol. 26, No. 8, 1073-1076 (1985); Tonew et al., Acta Virol., Vol. 36, 166-177 (1992)). These compounds all possess a pyroglutamate spiro β-lactone ring at one end of the molecule.
Although large numbers of therapeutically important polyketides have been identified, there remains a need to obtain novel polyketides that have enhanced properties or possess completely novel bioactivities. The complex polyketides produced by modular polyketide synthases are particularly valuable, in that they include compounds with known utility as antihelminthics, insecticides, immunosuppressants, cytotoxic, antiviral, antifungal or antibacterial agents. Because of their structural complexity, such novel polyketides are not readily obtainable by total chemical synthesis. The present invention addresses this need by providing a new class of polyene oxazole polyketide compounds with therapeutic activity.